Backround and Objectives The preferred antibiotic treatment of chronic Lyme disease, and that of chronic neuroborreliosis in particular, is still not fully defined. In an effort to develop improved and more reliable remedies for chronic Lyme disease, an eclectic treatment regimen has been designed. It includes two antibiotics that are highly effective against both acute and chronic Lyme disease ceftriaxone (2 g, IV, once a day, 30 days) and doxycycline (100 mg/kg, bid, per os, 60 days). The goal of this project is to assess the efficacy of this combination regimen, originally devised for humans, in rhesus macaques. More specifically, to monitor the elimination of a Borrelia burgdorferi infection from all organs commonly targeted by this spirochete, and especially from the central nervous system. Results Six rhesus macaques were inoculated with a neurotropic strain of B. burgdorferi (strain NT1) by exposure to infected ticks, and one control animal was exposed to the bite of uninfect ed ticks. All animals were confirmed to be infected by cultivating spirochetes, and amplifying spirochetal DNA by PCR, from skin biopsy samples. Animals were monitored over a six-month period. Unlike previous experiments, in which animals had been infected by needle inoculation with the NT1 strain, no evidence of infection in the central nervous system was obtained. Success in infecting the CNS may thus depend on the inoculum dose, which is likely higher when animals are infected with 108 spirochetes by needle inoculation than by exposure to the bites of ticks. Future Directions The antibiotic efficacy trial will now begin, but needle-inoculated animals will be employed. FUNDING NIH-NIAID RO1 AI42352-01 and Base grant. PUBLICATIONS None.